Improving the trans-ancestry portability of polygenic risk scores by prioritizing variants in predicted cell-type-specific regulatory elements
Author
Ishigaki, Kazuyoshi
Sugishita, Hiroki
Ohta, Tazro
Koido, Masaru
Matsuda, Koichi
Murakami, Yoshinori
Kawakami, Eiryo
Terao, Chikashi
Published Version
https://doi.org/10.1038/s41588-020-00740-8Metadata
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Amariuta, Tiffany, Kazuyoshi Ishigaki, Hiroki Sugishita, Tazro Ohta, Masaru Koido, Kushal Dey, Koichi Matsuda et al. "Improving the trans-ancestry portability of polygenic risk scores by prioritizing variants in predicted cell-type-specific regulatory elements." Nat Genet 52, no. 12 (2020): 1346-1354. DOI: 10.1038/s41588-020-00740-8Abstract
Poor trans-ancestry portability of polygenic risk scores is a consequence of Eurocentric genetic studies and limited knowledge of shared causal variants. Leveraging regulatory annotations may improve portability by prioritizing functional over tagging variants. We constructed a resource of 707 cell-type-specific IMPACT regulatory annotations by aggregating 5,345 epigenetic datasets to predict binding patterns of 142 transcription factors across 245 cell types. We then partitioned the common SNP heritability of 111 genome-wide association study summary statistics of European (average n ≈ 189,000) and East Asian (average n ≈ 157,000) origin. IMPACT annotations captured consistent SNP heritability between populations, suggesting prioritization of shared functional variants. Variant prioritization using IMPACT resulted in increased trans-ancestry portability of polygenic risk scores from Europeans to East Asians across all 21 phenotypes analyzed (49.9% mean relative increase in R2). Our study identifies a crucial role for functional annotations such as IMPACT to improve the trans-ancestry portability of genetic data.Other Sources
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049522/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37370941
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